Comparative analysis of macrophage interactions with antigens of tuberculous and non-tuberculous mycobacteria in vitro

Background. Ongoing research is investigating the interaction between mycobacteria and macrophages. Upon infection with mycobacteria, macrophages release cytokines. These include IFNy, TNF, IL-1, IL-6, and IL-12p40, among others. These substances play a critical role in the host response to tuberculosis and other mycobacterial infections. Aim. To investigate and compare the cytokine patterns produced by human macrophages in response to interaction with antigens from both pathogenic and conditionally pathogenic mycobacterial strains in vitro.

Methods. Blood monocytes were cultured for five days in the presence of 10 % active human serum. The resulting macrophages were then cultured with mycobacterial antigens from Mycobacterium tuberculosis, Mycobacterium avium, and Mycobacterium kansasii for 24 hours. Changes in macrophage gene expression profiles and the production of pro-inflammatory and anti-inflammatory cytokines were then assessed. A control group of “naive” macrophages cultured without any mycobacterial antigen was also used.

Results. Stimulation of human macrophages with antigens from different mycobacterial species resulted in the formation of distinct cell phenotypes: protective (M. tuberculosis), characterized by the expression of IL6, IFNG, and TNF; pro-inflammatory (M. kansasii), with active expression of IL6, IL1B, and TNF; and pro-inflammatory (M. avium), expressing IL6 and IL12. The cytokine production findings were fully consistent with the gene expression data.

Conclusion. These findings on macrophage-mycobacterial antigen interactions provide insight into the mechanisms by which both tuberculous and nontuberculous mycobacterial infections establish chronic macrophage infection.

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